This revised application pertains to the control of B cell development and differentiation in human newborns, in antibody-deficient patients and in patients who are reestablishing their specific immunity following a course of cytotoxic drug treatment. Relative immaturity of specific immunity in human newborns probably contributes to the severity of intra-uterine and neonatal infections. We propose to investigate the mechanisms of three functional characteristics of newborn lymphocytes: lack of T cell help, increased T cell suppression and B cell immaturity. Mitogen, T cell helper factors, adjuvants and mixed cultures will be used to identify the cell populations responsible for the overall limitation of the responses. We will test the proliferation and differentiation of antibody-deficient patients' B lymphocytes under similar conditions to determine whether their response is functionally immature. Following the cessation of anti-leukemic treatment, the number of B cells in blood and marrow returns to normal in 3 months but the frequency of pre-B cells in the marrow rises to above-normal levels for more than 9 months. We will explore, in rabbits and in man, the levels of pre-B cell regulation which these results suggest, including the role of T lymphocytes and the possible effects of deoxyadenosine. These studies will extend our understanding of immunity in infants with congenital infections, and in patients with primary or secondary antibody deficiency whose B cell development may be abnormal.